Fractalkine mediates T cell–dependent proliferation of synovial fibroblasts in rheumatoid arthritis

Sawai, Hirokazu; Park, Yong W.; He, Xing; Goronzy, Jörg J.; Weyand, Cornelia M.

doi:10.1002/art.22919

Cited by 54 publications

(49 citation statements)

References 43 publications

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“…Monocytes are also recruited in a chemotactic way by CCL2 respectively CX3CL1. CX3CL1 mediates T-cell dependent proliferation of synovial fibroblasts in RA (21). Within the scope of this comprehensive immunological network, neopterin concentrations reflect the activation degree of monocytes/macrophages and other immune cells and consequently the extent and activity of cellular immune activation (22).…”

Section: Resultsmentioning

confidence: 99%

Expression of Neopterin and Chemokines in Rheumatoid Arthritis and Cardiovascular Disease

Fagerer

Arnold²,

Bernatzky

et al. 2011

Pteridines

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In chronic inflammatory processes like rheumatoid arthritis (RA) and cardiovascular diseases (CVD) the role of pteridines and chemokines in the immune response is of great interest. The objectives of the study were to obtain information about an involvement of specific chemokines on the inflammatory process in patients with RA and CVD with activated production of the pteridine neopterin. 113 patients with RA according to American College of Rheumatology criteria including 24.8% suffering from CVD were included in the study (23% male, 77% female). For the assessment of monocyte activation and chemotaxis as well as the proinflammatory influence of chemokines on B-cells and angiogenesis in RA, neopterin and the chemokines CCL2, CXCL13 and CX3CL1 were measured by radio-and enzyme-immunoassays in serum. Neopterin and chemokines were all found in high concentrations. Neopterin significantly correlated with all chemokines: CXCL13 (r s = 0.368; p <0.0001), CX3CL1 (r s = 0.241; p <0.02), CCL2 (r s = 231; p <0.02), demonstrating high neopterin levels in RA patients to have a strong association to the chemokine induced chemotaxis of B-cells (CXCL13) and mononuclear cells (CX3CL1, CCL2). Significantly elevated concentrations of neopterin and CXCL13 were seen in patients with RA plus CVD compared to RA without CVD (p <0.03). The high incidence of cardiovascular diseases in rheumatoid arthritis seems to be associated with enhanced mononuclear (neopterin, CCL2) and B-cell activation (CXCL13), and as a consequence increased immune system activity.

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Section: Resultsmentioning

confidence: 99%

Expression of Neopterin and Chemokines in Rheumatoid Arthritis and Cardiovascular Disease

Fagerer

Arnold²,

Bernatzky

et al. 2011

Pteridines

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“…9 Fractalkine is found to function as a novel chemoattractant to induce OA fibroblast signaling. 10 Sawai et al 11 found that fractalkine mediates T cell-dependent proliferation of synovial fibroblasts in rheumatoid arthritis. In addition, fractalkine was found to activate the production of matrix metalloproteases (MMPs) including MMP-2, 12 and MMP-9 13 which is involved in the degradation of many different components of extracellular matrix (ECM).…”

Section: Introductionmentioning

confidence: 99%

Correlation of fractalkine concentrations in serum and synovial fluid with the radiographic severity of knee osteoarthritis

Zou

et al. 2013

Ann Clin Biochem

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Background: Fractalkine has been detected in synovial fluid (SF) from osteoarthritis (OA) patients. This study aims to examine the relation of fractalkine concentrations in serum and SF with the radiographic severity of OA. Methods: Fractalkine concentrations of serum and SF were measured using an enzyme-linked immunosorbent assay method in 223 patients with knee OA and 165 healthy controls. and 94.95 (76.46-106.68) vs. 80.34 (68.84-96.39) pg/mL, P ¼ 0.001, respectively]. Knee OA patients with KL grade 3 showed significantly elevated concentrations of fractalkine in SF compared with those with KL grade 2 [80.34 (68.84-96.39) vs. 74.31 (63.64-84.79) pg/mL, P ¼ 0.004]. Fractalkine concentrations in serum and SF of knee OA patients were both significantly associated with the disease severity evaluated by KL grading criteria (r ¼ 0.261, P < 0.001 and r ¼ 0.366, P < 0.001, respectively). Conclusion: The fractalkine concentrations in serum and SF may serve as an effective biomarker for the severity of OA.

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“…Darüber hinaus wird durch diese Interaktion eine T-Zell-Kostimulation im Sinne einer Produktion proinflammatorischer Zytokine durch synoviale Fibroblasten hervorgerufen [9]. Umgekehrt wurde beobachtet, dass die Proliferation synovialer Fibroblasten in Anwesenheit von CD4-positiven T-Zellen, die aus dem peripheren Blut betroffener RA-Patienten isoliert wurden, deutlich gesteigert ist und dieser Effekt durch die Zugabe eines monoklonalen Antikörpers gegen den Fraktalkine-Rezeptor blockiert werden kann [10]. Dies legt die Hypothese nahe, dass durch die CX3CL1-CX-3CR1-vermittelte Interaktion zwischen T-Zellen und synovialen Fibroblasten die Proliferation synovialer Fibroblasten stimuliert wird.…”

Section: Funktionelle Bedeutung Von Fraktalkine In Der Pathogenese Deunclassified

“…In vitro konnte durch die Gabe des Anti-CX3CR1-Antikörpers die T-Zell-abhängige Proliferation synovialer Fibroblasten gehemmt werden [10]. Darüber hinaus konnte durch die Gabe des monoklonalen Anti-Fraktalkine-Antikörpers die CX3CL1-vermittelte Stimulation der MMP-2-Produktion in synovialen Fibroblasten blockiert werden [3].…”

Section: Fraktalkine-inhibition -Eine Neue Therapiestrategie Bei Ra?unclassified

Fraktalkine – ein proinflammatorisches Chemokin bei rheumatoider Arthritis

Blaschke

Müller

2008

Z. Rheumatol.

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Fractalkine (CX3CL1), so far the only member of the CX3C class of chemokines, and its receptor, CX3CR1, are strongly expressed in the chronically inflamed synovial tissue of patients with rheumatoid arthritis (RA). Due to the specific binding of Fractalkine to its receptor, many proinflammatory reactions involved in the pathogenesis of RA are triggered. Functionally, fractalkine plays an important proinflammatory role in RA pathogenesis as characterized by induction of synovial angiogenesis, chemotaxis, activation of monocytes and T cells as well as the stimulation of proliferation and synthesis of matrix degrading enzymes (matrix metalloproteinases, MMP) in synovial fibroblasts. Fractalkine thus may represent a novel target molecule for therapeutic intervention in RA.

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Fractalkine mediates T cell–dependent proliferation of synovial fibroblasts in rheumatoid arthritis

Cited by 54 publications

References 43 publications

Expression of Neopterin and Chemokines in Rheumatoid Arthritis and Cardiovascular Disease

Expression of Neopterin and Chemokines in Rheumatoid Arthritis and Cardiovascular Disease

Correlation of fractalkine concentrations in serum and synovial fluid with the radiographic severity of knee osteoarthritis

Fraktalkine – ein proinflammatorisches Chemokin bei rheumatoider Arthritis

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